Medical Science

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An investigation into the causes of illness in the 1996 Dusi canoe marathon.
(1997) Foreman, S. E.; Mars, Maurice.
Abstract available in PDF.
The role of vitamin A (retinol palmitate) and beta-carotene on B- lymphocytes and natural killer cells in HIV-1 seropositive pregnant women.
(1998) Doorasamy, Trevor.; Coovadia, Hoosen Mahomed.
Abstract available in PDF.
A retrospective analysis of induction of labour at a regional hospital in KwaZulu-Natal, South Africa.
(2012) Malende, Brenden.; Kambaran, A.
Abstract available in PDF file.
Computational studies of pentacycloundecane peptide based HIV-1 protease inhibitors.
(2013) Chibi, Buyisile.; Soliman, Mahmoud Elsayed Soliman.; Kruger, Hendrik Gerhardus.; Govender, Thavendran.; Maguire, Glenn Eamonn Mitchel.
Abstract available in PDF.
Drug susceptibility testing of second and third line anti-tuberculosis drugs used in the management of extensively drug resistant tuberculosis.
(2013) Moodley, Salona.; Moodley, Prashini.
Drug resistant tuberculosis is a major contributor to South Africa’s quadruple burden of disease. Management of this infection in a highly HIV endemic area is a constant challenge. There is a paucity of new anti-tuberculosis agents in the developmental and clinical trial phases to address the problem of extensively-drug resistant tuberculosis (XDR-TB). In an attempt to affect a cure in patients with XDR-TB, it has become necessary to re-introduce previously used anti-tuberculosis drugs, as well as antimicrobial agents designed for treatment of non-tuberculosis infections. Whilst these drugs may have previously been tested and shown efficacy in drug susceptible tuberculosis, their activity in XDR TB strains was not tested before introduction for management of XDR-TB in KwaZulu-Natal, South Africa. Drug susceptibility testing (DST) plays an integral role in the diagnosis and treatment options for tuberculosis. It is able to decrease the burden and spread of resistant tuberculosis. However DSTs methods for second line anti –TB drugs (SLDs) and third line anti-TB drugs (TLDs) have not been standardised. Critical concentrations of these anti-TB drugs remain unknown or vary within and between settings thus further hampering the control of TB.
Identification of anti-cancer agents using integrated computational tools.
(2015) Mbatha, Sbongile Happyness.; Soliman, Mahmoud Elsayed Soliman.
Cancer is a heterogeneous disease that is responsible for various molecular changes and pathological entities that play vital roles in its response to treatment, survival, and growth. Better understanding into the critical pathways and molecular events involved in cancer has enabled the identification of novel targets and development of anti-cancer therapies. In this study, two enzymes that have been shown to be involved in different stages of cancer were used, namely cathepsin B and Hsp90. The main aim of this study was to employ integrated in-silico approaches to study inhibitory routes of these enzymes to develop novel anti-cancer agents. Cathepsin B is the most well studied of the cathepsin family as a potential therapeutic target to treat cancer. To accomplish practical aim 1 of this study, the Michael-acceptor type compounds obtained from a chemical database that irreversibly inhibit cathepsin B were investigated. Validation was carried out using compounds with experimentally determined anti-cathepsin B activity. Four novel compounds exhibited better covalent binding affinity when compared against the experimentally determined prototypes. Molecular dynamics simulations were performed to ensure the stability of the docked complexes and to allow further analysis. Per-residue interaction decomposition analysis provided deeper insight into the interaction themes with active site residues. It was found that polar and hydrophobic interactions had the highest contribution towards drug binding. Recent experimental studies have documented FDA-approved protease inhibitors involvement in anti-cancer activity, however, there was limited understanding to the mode of inhibition. To accomplish practical aim 2 of this study, the mode of inhibition of protease inhibitors against Hsp90 cysteine protein was investigated. The lack of an X-ray crystal structure of human Hsp90 prompted the creation of its homology model for subsequent simulations. Two possible binding sites, C-terminal and N-terminal domains, were identified and considered in this study. Molecular docking followed by molecular dynamic simulations and post-dynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 protease inhibitors against human Hsp90. Our findings from thermodynamics calculations revealed that these inhibitors were more likely to bind to the N-terminal domain (~ 54.7 -83.03 kcal/mol) when compared to C-terminal domain. This appears to be the first account of a detailed computational investigation aimed to understand the binding mechanism of HIV protease inhibitors binding to Hsp90. Information gained from this study should also provide a significant route map towards the design and optimisation of potential derivatives of protease inhibitors to treat breast cancer. The results obtained will serve as a powerful tool in the drug design and development process. However, further experimental investigations will be useful to improve our computational findings.
Tissue distribution of an anti-TB drug, TBA-354 in rats via mass spectrometric investigations.
(2016) Ntshangase, Sphamandla.; Govender, Thirumala.; Kruger, Hendrik Gerhardus.; Maguire, Glenn Eamonn Mitchel.
Tuberculosis (TB) (TB) is one of the most well-recognized ancient human diseases in the history of mankind and it remains the major cause of human death amongst the transmittable diseases despite the use of antitubercular antibiotics. TB is caused by a pathogenic bacterium known as Mycobacterium tuberculosis (M.tb). The M.tb bacteria primary site of infection is the human lungs (resulting in pulmonary TB) but it can also affect other body parts (extrapulmonary TB) such as the bones, central nervous system (CNS), liver and many more others. Present-day TB research is focused on the development of more effective anti-TB drugs that can help shorten the treatment period. One of the major set-backs in TB drug development is to find the balance between the potential drug’s side effects and its activity. The present demonstrates the potential of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) techniques in the evaluation of the fundamental in-vivo pharmacokinetics and tissue distribution properties of a bicyclic nitroimidazole derivative, TBA-354. This drug is recognized to have an excellent activity against M.tb strains but also known to have mild signs of neurotoxicity. The use of MSI in this study shows the exact localization and accumulation of the drug in the brain, providing evidence as to why it showed certain neurotoxic signs during clinical trials. The study was conducted on healthy female Sprague-Dawley rats by administering 20 mg/kg of the drug, via an intraperitoneal (i.p.) route. After dosing the biological samples (plasma, lungs and brain) were collected at different time points for analysis. A validated LC-MS/MS method was used to quantify TBA-354 in rat plasma, lung and brain homogenate samples. LC-MS/MS cannot provide enough information regarding the drug localization and where it accumulates in the brain, therefore, MSI was then used to study the accumulation of the drug in different regions of the brain. As per LC-MS/MS results, the drug showed significant pharmacokinetic and distribution properties in the rat model with the highest levels in plasma compared to lung and brain. MALDI-MSI results showed that the drug was effectively able cross the blood-brain barrier (BBB) resulting in toxic accumulation in the neocortical regions of the brain. This study has proven the efficacy of MSI as a suitable analytical technique that can be used in future preclinical studies to evaluate the neurotoxicity of drugs targeting the brain, thus minimizing possible side effects.
Evaluation of the left ventricular ejection fraction post right ventricular pacing at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, KwaZulu-Natal (KZN).
(2016) Kasipersad, Sherlina.; Magula, Nombulelo Princess.
Since the implantation of the first artificial pacemaker in 1958, these devices have become the treatment of choice in bradycardias. Despite its widespread use, only a few studies have looked at the effects of single chamber right ventricular(RV) pacing on left ventricular(LV) function in patients with sinus node dysfunction or atrioventricular node dysfunction. In addition, these studies have produced conflicting results with no consensus reached. Furthermore, the limitation to these studies were the small sample sizes and the absence of sequential echocardiographic monitoring of LV function in each patient. To the best of the authors’ knowledge, no such studies have been conducted in South Africa. This study reviewed data collected from Inkosi Albert Luthuli Central Hospital (IALCH), which is a government hospital in Durban, KwaZulu-Natal (KZN), South Africa. The objective of the study was to evaluate the effects of RV pacing on LV function in a setting where the majority of patients requiring a permanent pacemaker receive single chamber RV apical pacing. The focus of this study was to assess the effect of RV pacing on LV function by assessing the ejection fraction(EF), on echocardiography, pre and post pacemaker insertion. A retrospective chart review of 465 patients managed at the IALCH pacemaker clinic from 2003 up to 2012 was undertaken. Adult patients 18 years and older with a documented EF at the time of insertion of a pacemaker were included in the study. Patients were excluded from the study if they had coronary artery disease (CAD), unrepaired valvular heart disease, atrial fibrillation or dual chamber pacemakers. After enforcing the exclusion criteria, 430 patients were excluded and only 35 patients were eligible for the study. LV dysfunction was pre-defined as a left ventricular ejection fraction (LVEF) of < 50%. This study showed that RV pacing did not have a statistically significant effect on LV function post pacemaker insertion, based on the assessment of EF. The study was limited by the low number of eligible patients as it was a retrospective study and obtaining data was difficult as most patients who require a pacemaker do not routinely have a baseline echocardiograph done prior to insertion of the pacemaker. Another limiting factor in the study was that EF was the only modality of LV function that was assessed. Moreover, evaluation of the EF on echocardiography is subjective and user dependent. International studies have shown that the site of RV pacing has an impact on the degree of LV dyssynchrony and function. This factor could not be assessed in the current study as the site of RV pacing was not documented and was not standardised. Pacing in the correct clinical context is a necessity and is lifesaving. Current literature shows that RV pacing is a safe, relatively simple, convenient procedure that is well tolerated and is effective. This study showed no deterioration in LV function in patients post RV pacemaker insertion, which is important as the RV remains the most common site of lead placement especially in the resource limited state sector. Some studies have reported that RV pacing is associated with LV dysfunction. However, since there is a paucity of level 1 evidence regarding this aspect of RV pacing, the need for prospective studies on the long-term effects of RV pacing on LV function is required. In addition, the impact of alternative pacing sites on LV function should be explored.
Genital tract immune activation, inflammation and sexually transmitted infections in CAPRISA 008 trial participants.
(2016) Mhlungu, Sanele Nobleman.; Liebenberg, Lenine Julie.; Ngcapu, Sinaye.
Abstract available in PDF file.
The role of endoplasmic reticulum stress in shedding of syncytiotrophoblast microparticles in pregnant black South African women.
(2016) Verma, Sonal Raj.; Mackraj, Irene.
Background and aim: Preeclampsia, accounts for the majority of maternal deaths emanating from hypertension in pregnancy. Although its exact aetiology is unclear, endoplasmic reticulum (ER) stress and trophoblast apoptosis are implicated. The placental microenvironment in preeclampsia is hypoxic and induces the expression of Hypoxia inducible factor-1 alpha (HIF-1 α) and CHOP (C/EBP homologous protein) which are activated due to ER stress. Hypoxia-induced oxidative and endoplasmic reticulum stress initiate a cascade of apoptotic events with the consequential shedding of microparticles which mediate the peripheral maternal syndrome of preeclampsia. The main aim of the study was to immuno-localise the expression of HIF-1 α and CHOP in placental tissues and concomitantly characterise and quantify the syncytiotrophoblast microparticles in the maternal circulation. Materials and Methods: Plasma and placental tissue were obtained from normotensive and pre-eclamptic pregnant women. The expression of HIF-1α and CHOP was analysed using immunohistochemistry. Microvesicles in maternal circulation were isolated and their size distribution was determined using nanoparticle tracking analysis. The relative concentration of syncytiotrophoblast microvesicles (STBMs) from isolated microvesicles was determined using Placental Alkaline Phosphatase ELISA. Results: This study demonstrated an increased immuno-expression of HIF-1 α and CHOPS in preeclampsia compared to the controls (p < 0.05). Additionally, a significant increase in the mean syncytiotrophoblast microparticles concentration was observed in PE, compared to the controls (p < 0.05). Further analysis showed a positive correlation between the immunohistochemical expression of HIF-1 α and CHOP and the STBMs concentration. Conclusion: This study demonstrates increased placental-expression of HIF-1α and CHOP in preeclampsia compared to normotensive pregnancies which directly relate to the increase syncytiotrophoblast microvesicles concentration in maternal circulation. These findings indicate that placental hypoxia and ER stress are contributory factors to the pathogenesis of PE and may be a key contributory factor in placental cell apoptosis and the consequent release of placental derived debris into the maternal circulation. Key words: HIF-1α; CHOP; Syncytiotrophoblast Microvesicles; Pre- eclampsia; Endoplasmic Reticulum Stress; Hypoxia
Whole transcriptome analysis to elucidate the role of mtp in gene regulation of pulmonary epithelial cells infected with Mycobacterium tuberculosis.
(2016) Dlamini, Mlungisi Thabiso.; Pillay, Manormoney.
Abstract available in PDF file.
Genetic mechanisms of D-cycloserine resistance.
(2016) Munsamy, Vanisha.; Pym, Alexander S.
Abstract available in PDF file.
Benign uterine conditions: correlating MRI and US findings: retrospective analysis of 33 patients.
(2016) Ramaema, Dibuseng Paulina.
Abstract not available.
Anatomic study of the morphologic relationship between the proximal left and right coronary arteries.
(2016) Singh, Sadhna.; Satyapal, Kapil Sewsaran.; Lazarus, Lelika.; Ajayi, Nasirudeen Oladipupo.
Arising from the aorta, the right (RCA) and left (LCA) coronary arteries provide the arterial supply to the heart. An extensive literature review revealed that most studies have either evaluated the morphology of the RCA or the LCA independently. This study aimed to document the relationship between the morphology of the RCA and LCA using coronary angiograms and fetal dissections. In addition, variations such as split or double RCA and absence of the LCA was documented. A review of 500 coronary angiograms and a fetal dissection of 41 heart specimens was conducted. The RCA and LCA were classified according to their branching patterns and arterial dominance. The embryologic relationship between the RCA and the LCA was also documented including their lengths and diameters. The angiographic review showed that the most prevalent branching pattern of the LCA was bifurcation in 65.8%, while trifurcation and quadrifurcation occurred in 20.4% and 1.6%, respectively. The splitting of the RCA and absence of the LCA occurred in 4.2% and 11.8%, respectively. A significant correlation was found between the split RCA and absent LCA showing that the split RCA was more prevalent in the absence of the LCA. The dissection of the fetal heart specimens (age range 13.13 - 26.95 weeks) found that the RCA arose from the right aortic sinus and provided arterial dominance in all the specimens. The LCA was classified into types according to their branching pattern. The bifurcation, trifurcation and quadrifurcation of the LCA occurred in 68.3%, 29.3% and 2.4% of hearts, respectively. The mean lengths of the RCA and LCA were 0.98 ± 0.54mm and 1.83 ± 0.77mm, respectively. The mean diameters of the RCA and LCA were 0.38 ± 0.12mm and 0.49 ± 0.17mm, respectively. A significant correlation was found between the RCA and LCA length and the fetal age indicating changes in the development of the coronary vasculature with fetal development. A knowledge of the distribution of the RCA and LCA assists in providing information on the area of the myocardium supplied. With the advent of coronary angiography, a comprehensive understanding of coronary arterial anatomy and their variations is necessary.
Molecular characterization of resistance and virulence in Methicillin Resistant Staphylococcus Aureus (MRSA) from the private sector in KwaZulu-Natal, South Africa.
(2016) Amoako, Daniel Gyamfi.; Esaack, Sabiha Yasuf; Bester, Linda Antionette.
Abstract available in PDF file.
Antimicrobial susceptibility testing of four 5-nitroimidazoles against trichomonas vaginalis.
(2016) Mtshali, Andile.; Joubert, Bronwyn C.
Abstract available in PDF file.
Extrapulmonary tuberculosis at King Edward hospital : a descriptive retrospective study.
(2016) Gounden, Strinivasen.; Magula, Nombulelo Princess.
Background Globally, South Africa remains one of the top twenty high tuberculosis(TB) burden countries. In addition, South Africa has the highest burden of tuberculosis/Human Immunodeficiency virus (TB/HIV) coinfection in the world, with the province of KwaZulu-Natal representing the global epicenter of TB/HIV. With the scaling up of one of the world’s largest antiretroviral therapy programs, it was envisioned that the burden of tuberculosis would be reduced. While significant progress has been made to improve the diagnosis of pulmonary tuberculosis, the diagnosis of extrapulmonary TB(EPTB) remains a significant challenge in resource constrained settings. This study describes the profile of patients with EPTB at a tertiary hospital in a TB/HIV hyperendemic setting in Durban, South Africa. Methods A retrospective chart review was conducted, and included all adult patients diagnosed with EPTB at a tertiary hospital in Durban, South Africa, between 1 January 2016 and 31 March 2016. Data was extracted from the facility TB register, as well as patient clinical records. All data was analysed using SPSS software (SPSS 23.0, Armonk NY: IBM Corp). For all statistical comparisons, a 5% level of significance was used; correspondingly 95% confidence intervals were used to describe effect size. All data was assessed for normality, and non-parametric tests were used where necessary. Medians and interquartile ranges were used for data not amenable to parametric description. Pearson’s Chi-square test was utilised for comparison between subgroups. All p values were 2-tailed and considered significant below 0.05. Significant findings were analysed for association using Phi and Kramers V test for symmetric measures. Results There were 188 new cases of TB during the study period, with 80 patients diagnosed with EPTB. The mean age of patients was 34.73 years (SD ±9.44). Forty two (52.5%) patients were female, while 76(96%) were black African. The most common risk factor for EPTB was HIV co-infection (88.8%). The median CD4 cell count was 68 (IQR 32-165) cells/mm3. Pleural (36.3%), lymph node (28.7%) and abdominal(27.5%) involvement were the most common sites of extrapulmonary disease Eleven of the 80 patients (13.8%) presented with EPTB involving more than one anatomical system. Weight loss, fever, night sweats and cough were amongst the most common symptoms reported. Signs varied according to the site of infection. Non-specific symptoms were common. In the majority of cases, more than one diagnostic method was used to confirm the presence of TB in distant organs. Conclusion A high index of suspicion is required when assessing a patient with known risk factors for EPTB. Immunosuppression remains the most significant risk factor for the development of EPTB. In our setting, HIV co-infection remains the most common risk factor. Advancements in Xpert MTB/Rif and computer tomography have greatly assisted in rapidly diagnosing EPTB. Despite improved access to antiretroviral therapy over the past years, advanced HIV disease remains a significant challenge to eradicating TB.
Case series of subtotal exenteration with buccal mucosal graft for orbital squamous cell carcinoma.
(2016) Surajballi, Sharisha.; Kruse, Carl-Heinz.
The aim of the study was to look for a safe alternative to a disfiguring total orbital exenteration for orbital squamous cell carcinoma, so that a standard hospital issue inexpensive stock ocular prosthesis can be fitted with improved aesthetic results, rather than an expensive custom made prosthesis for the patient’s own cost. The subjects and methods involved a retrospective case review which was performed of patients from St Aidan’s Missionary Hospital initially, which was later amalgamated into the McCords Provincial Eye Hospital, Durban, KwaZulu-Natal, South Africa. Ten consecutive patients who underwent an ‘extended’ lid-sparing subtotal exenteration with minimally preserved healthy conjunctiva and a buccal mucosal graft were identified over a 3 year period from 1 January 2011 to 31 December 2013. Patients’ clinical records were reviewed. Results included all of the ten patients having a good aesthetic outcome at 4 weeks and six months with a standard hospital issue stock ocular prosthesis. One patient had a repeat buccal mucosal graft after forniceal shortening. Three patients had local recurrences within one year but all recurrences were identified easily and total exenteration was successfully performed. The survival rate at 3 years was ninety percent as one patient was lost to follow-up. A subtotal orbital exenteration with minimally preserved healthy conjunctiva and a buccal mucosal graft is cost effective, safe and cosmetically acceptable with a standard ocular prosthesis.
“Sugars”: the chemical characterization of a prevalent illicit drug cocktail in South Africa.
(2016) Chetty, Yvette Yolanda.; Nadar, Anand.
ABSTRACT Introduction “Sugars” is an illicit drug cocktail that is thought to be a mixture of heroin, cocaine and other substances in order to add bulk to the final product. Since its emergence in a local KwaZulu-Natal community known as Chatsworth in 2006, the use of the drug has spread to other provinces in South Africa and has currently become a popular drug amongst the youth. The affordability of the cocktail has allowed it to become rampant in low income communities and this coupled with its accessibility further reinforces “Sugars” as the preferred drug of choice. The use of the drug allows the user to experience euphoria, however once the effects wear off, the pain of the resulting withdrawal or “roster” drives the individual to continue using the drug. The withdrawal symptoms range from common cold and flu-like symptoms to extreme bone pain, stomach cramps, constipation and nausea. There have been attempts at rehabilitating “Sugars” addicts however, due to the lack of knowledge of a precise chemical composition of the cocktail, it is difficult to effectively maintain therapeutic interventions. Aim The aim of this study was therefore to chemically characterize the composition of “Sugars”, thereby allowing for the development of targeted treatment options for rehabilitation centres. Method Batches of samples of the mixture were sourced from 3 independent suppliers in the Durban South area of KwaZulu-Natal, South Africa. Chromatographic techniques were used to separate the individual constituents of the mixture and determine molecular weights of these compounds. Nuclear magnetic imaging was used to identify the compounds. Results and discussion The tests confirmed the presence of heroin, papaverine and noscapine in the “Sugars” samples analysed. However, there was variance noted in the composition between the different sources of the drug. We hypothesize that “Sugars” was therefore not heroin that is bulked up with other substances, but may be the waste product of the final purification process in the illicit heroin manufacturing process. Conclusion It was concluded that “Sugars” contained heroin, noscapine and papaverine. The variance in composition of heroin in the samples suggests independence between suppliers. The presence of papaverine and noscapine, which are impurities that are usually removed during the final purification of heroin, supports the hypothesis that “Sugars” is the waste product of the manufacture of heroin. Noscapine and papaverine are costly pharmaceutical products and we therefore speculate that it would not be economically viable to bulk up a cheap low grade drug cocktail with these compounds.
Defining current facial fracture patterns in a quaternary institution following high-velocity blunt trauma.
(2016) Magagula, Senzwesihle Clive.
Background: In the early 20th century, René Le Fort studied facial fractures resulting from blunt trauma and devised a classification system still in common use today. This classification, however, was based on low-velocity trauma. In modern practice, in a quaternary-level referral hospital, patients are often admitted following high-velocity injuries that mostly result from motor vehicle collisions. Objectives: A retrospective study to define facial bone fractures occurring subsequent to highvelocity trauma. Method: A retrospective study comprising the review of CT scans of 52 patients with highvelocity facial fractures was performed between April 2007 and March 2013. Injuries were classified using the Le Fort classification system. Deviations from the true Le Fort types, which are often depicted in the literature as occurring bilaterally and symmetrically, were documented; these included unilaterality, occurrence of several Le Fort fractures on one side of the face, occurrence of several Le Fort fractures on different levels and on different sides of the face, and occurrence of other fractures in addition to Le Fort fractures. Results: Of the 52 cases, 12 (23%) had Le Fort injuries, with true Le Fort fractures occurring in only 1, and 11 deviating from the classic description. Nine patients had Le Fort fractures and additional fractures. Mandibular and zygomatic bone fractures were found to be common associations with Le Fort injuries, occurring in 58% and 33% of the cases respectively. Conclusion: Fractures occurring in modern practice often deviate from the traditional Le Fort classification. Precise recognition of these deviations and recognition of additional associated fractures is pivotal in their management, assisting the surgeon in determining the treatment plan, such as the surgical approach and the order in which to fix the various fractured components.

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